MCP-1 licenses mesenchymal stem cells for T-cell-supportive function

Abstract Mesenchymal stem cells (MSCs) exhibit dynamic immunomodulatory capacity, transitioning between immunosuppressive and immunosupportive states in response to microenvironmental cues. However, the molecular signals that regulate this functional plasticity across diverse MSC populations remain poorly defined. Here, we report that monocyte chemoattractant protein-1 (MCP-1) promotes a T-cell-supportive phenotype in selected MSC populations (such as MSCs from bone marrow, adipose tissue, pancreas, and gingiva). In CTX-induced immunosuppressed mice, MCP-1-pretreated selected MSCs protected T cells from apoptosis and partially restored lymphoid organ atrophy. In vitro, MCP-1 inhibited IFN-γ binding to TLR2 and promoted CXCL10 expression in LNMSCs, supporting T-cell survival and proliferation. SPR confirmed dose-dependent MCP-1–TLR2 binding, and molecular dynamics simulations provide a computational structural rationale for this interference. These findings identify MCP-1 as a promoter of T-cell-supportive function in selected MSC populations, with responses dependent on tissue source and cellular context.